This Funding Opportunity Announcement (FOA) requests
applications for a new research consortium, the Consortium on Beta cell Death
and Survival (CBDS). The mission of CBDS will be to better define and detect
the mechanisms of beta cell stress and destruction central to the development
of T1D in humans, with the long-term goal of protecting the residual beta
cell mass in T1D patients as early as possible in the disease process. CBDS
will be part of the Human Islet Research Network (HIRN).

Key Dates

Posted Date

September 26, 2013

Open Date (Earliest Submission Date)

January 27, 2014

Letter of Intent Due Date(s)

January 27, 2014

Application Due Date(s)

February 27, 2014, by 5:00 PM local time of applicant
organization.

Applicants are encouraged to apply early to allow adequate
time to make any corrections to errors found in the application during the
submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

June/July 2014

Advisory Council Review

October 2014

Earliest Start Date

December 2014

Expiration Date

February 28, 2014

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed to do otherwise (in
this FOA or in a Notice from the NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the FOA)
is required and strictly enforced. Applicants must read and follow all
application instructions in the Application Guide as well as any program-specific
instructions noted in Section IV. When
the program-specific instructions deviate from those in the Application Guide,
follow the program-specific instructions. Applications that do not
comply with these instructions may be delayed or not accepted for review.

This Funding Opportunity Announcement (FOA) requests applications
for a new research consortium, the Consortium on Beta cell Death and Survival
(CBDS). The mission of CBDS will be to better define and detect the mechanisms
of beta cell stress and destruction central to the development of T1D in humans,
with the long-term goal of protecting the residual beta cell mass in T1D
patients as early as possible in the disease process. The CBDS will be part of a
collaborative research framework, the Human Islet Research Network (HIRN) that
will include four research consortia and an Administrative Hub composed of a
Bioinformatics Center and a Coordinating Center. HIRN's overall mission will be
to support innovative and collaborative translational research to understand
how human beta cells are lost in T1D, and to find innovative strategies to
protect and replace functional beta cell mass in humans. In order to maximize
scientific exchanges and accelerate research in that field, it is expected that
all information, data, biomaterials, models, protocols, reagents, resources and
methods developed by CBDS investigators will be shared not only within CBDS, but
also with other HIRN investigators and with the research community.

Background

The
NIDDK Human Islet Research Network (HIRN)

Starting in 2014 NIDDK will establish a new team science
program, the Human Islet Research Network (HIRN), to help organize and support
collaborative translational research related to the loss of functional beta
cell mass in Type 1 Diabetes (T1D). HIRN will be jointly supported by NIDDK and
the type 1 diabetes special funding program, and its overall mission will be to
better understand how human beta cells are lost in T1D, and to find innovative
strategies to protect or replace functional beta cell mass in diabetic patients.
This program will be configured as a modular network of small research
consortia, each defined by a specific set of research priorities. The network
structure will help to facilitate interactions between small communities of
investigators organized around common biological and/or technological
challenges, with the overall goal of developing innovative strategies for the
treatment, prevention and monitoring of T1D.

HIRN will be initiated through issuance of six related funding
opportunity announcements, and will use a Cooperative Agreement funding
mechanism. Two complementary initiatives will provide the administrative
structure needed to support HIRN activities through the creation of an
Administrative Hub (HIRN-AH) composed of a Coordinating Center (HIRN-CC; RFA-DK-13-013)
and a Bioinformatics Center (HIRN-BC; RFA-DK-13-014).
Four independent research initiatives will invite four founding consortia, each
supporting investigator-initiated projects in the following areas: Targeting
and Regeneration (CTAR; RFA-DK-13-015),
Human Islet Biomimetics (CHIB; RFA-DK-13-016),
Modeling Autoimmune Interactions (CMAI; RFA-DK-13-017)
and Beta Cell Death and Survival (CBDS; RFA-DK-13-018).

All HIRN research initiatives put a strong emphasis on human
disease biology, the use of human cells and tissues, and the development of
reagents, tools and disease-modeling platforms that can help further our understanding
of the human disease process, or lead to innovative treatment strategies for
patients with severely depleted beta cell mass. Beyond the set of six founding
FOAs issued in 2014, it is anticipated that additional HIRN initiatives may be
issued in future years, provided availability of funds, to support the
evolution of the program over time, and in response to emerging scientific and
technological advances.

Consortium
on Beta-cell Death and Survival (HIRN-CBDS)

Type 1 Diabetes (T1D) is a progressive immune-mediated
disease that is preceded by an asymptomatic preclinical period of highly
variable duration in humans. In addition to genetic susceptibility, it is
believed that biological or environmental triggers contribute to the initiation
and development of T1D, leading to the progressive disappearance of functional
beta cells from the pancreatic islet, and to the development of an autoimmune
response targeting specifically and exclusively insulin-producing beta cells.

Understanding beta cell dysfunction and beta cell loss
during the period of asymptomatic or "silent" T1D that takes place in
genetically susceptible individuals, with or without multiple T1D
autoantibodies, may provide critical insight into the respective contribution of
metabolic stress, inflammation or other pathogenic processes to beta cell
injury, and ultimately to the development of autoimmune T1D. A more thorough
mechanistic understanding of these early steps could lead to novel therapeutic
solutions to protect and renew the population of residual beta cells present in
recent-onset T1D patients. Moreover, the development of a new generation of
highly-sensitive, highly-specific biomarkers that can reliably report on the
subtle changes in beta cell stress, damage or death during the asymptomatic
period could lead to early therapeutic interventions in at-risk individuals
that delay or even prevent the development of autoimmunity.

T1D is a difficult disorder to investigate, given the
absence of reliable methods for early detection, the heterogeneity of the human
disease, and the lack of access to the target organ in living individuals.
Historically, investigations have either examined indirect features of the
disease in patients with T1D, or used animal models to dissect pathogenic mechanisms.
In that respect, the non-obese diabetic (NOD) mouse has been used effectively
to formulate hypotheses regarding disease onset and progression. However,
recent studies using cadaveric human pancreata are pointing to important
differences between mice and humans with respect to the mechanisms underlying
the loss of beta cells in early T1D. Most of these pioneering studies have used
pancreatic specimens collected by the Network for Pancreatic Organ Donors with
Diabetes (nPOD) that was established to recover and characterize pancreata and
related organs from donors with various risk levels for type 1 diabetes (T1D),
including donors with recent disease onset and asymptomatic donors with T1D
autoantibodies. The pathological analyses of these tissues point to unique
characteristics of the human pancreas at disease onset, including decreased
pancreatic size and exocrine atrophy; paucity or absence of insulitis; lobular
loss of beta cells in pancreatic regions where insulitis does exist; diminished
insulin content in remaining beta cells; and heterogeneity of the pancreatic
pathological profile between organ donors. Altogether, these observations
suggest that multiple mechanisms may lead to the loss of functional beta cells
and contribute to the pathogenesis of T1D in humans.

An early and reliable identification of individuals who are
entering asymptomatic T1D would greatly facilitate the study of the initial
phase of the disease and the development of therapeutic strategies to stop the
progression towards autoimmunity. At present, the detection of multiple autoantibodies
is the best biomarker of T1D risk, but it also provides proof that the
autoimmune process is already floridly active. For that very reason, even the
discovery of new antibodies against other native islet epitopes (autoantigens)
is unlikely to yield biomarkers that report on the initiation of the disease
process. However, recent studies in stressed islets (mouse and human) have
identified defects in the beta cell transcriptional and translational
machineries that could provide highly-specific biomarkers of early T1D. Beta
cell stress causes the formation of many specific or deficient cell products, including
miRNAs; abnormally spliced mRNAs resulting in modified protein isoforms;
inappropriately folded, cleaved or posttranslationally-modified native
proteins; and aberrant products resulting from dysfunctional ER-associated
degradation pathways. Some of these modified peptides and proteins can be
turned into neo-antigens that are specific of early beta cell injury, and may
prime the autoimmune process in T1D. miRNA patterns in human diseases are often
tissue-specific, and miRNAS display unusually high stability in formalin-fixed
tissues as well as in plasma, serum and saliva, and are easy to detect with a
high degree of specificity. The release in the bloodstream of some of these beta
cell stress-induced products, or the generation of antibodies against
neo-antigens of the stressed beta cell, may constitute highly-specific
biomarkers of the earliest events leading to T1D.

Based on recent developments in islet biology research, several
assumptions about early stages of the disease process in humans may have to be
revisited. For example, it is still widely accepted that the reduction of functional
beta cell mass in T1D results from a massive beta cell destruction that starts
during the asymptomatic phase. But other mechanisms may contribute to the
progressive "disappearance" of functioning beta cells in the islets
of patients with T1D, at least in the early stages. Recent studies on islet
plasticity indicate that beta cell stress and dysfunction can result in the dedifferentiation
of mature beta cells into "progenitor-like" cells. The relative
contribution of a variety of mechanisms (apoptosis, necrosis, autophagy,
de-differentiation, autoimmune destruction) to the reduction in beta cell
number during the asymptomatic phase, and the contribution of the various cell
types present in the pancreatic compartment (such as cells of exocrine,
endocrine, neuronal or immune origin) to the early disappearance of beta cells,
need to be explored anew in the context of human pathology. In that regard, the
tissue heterogeneity that characterizes many human pancreata around the time of
clinical presentation represent a rich experimental opportunity, since islets
where the beta cells have disappeared, islets where beta cells are being
eliminated, and islets where beta cells are still intact are often found
together within a single biopsy.

CBDS will encourage the use of human pancreata and related
tissues with the goal of providing a definition of the pathogenic mechanisms
leading to the demise of beta cells in patients with T1D. It is expected that
this information will assist in the development of improved biomarkers for the
asymptomatic phase of human T1D. CBDS will also support the development of new
technologies and methods that will help investigators extract complex
biological information from unfavorable material such as paraffin-embedded or
frozen tissues obtained from cadaveric donors, to help answer fundamental
questions about the early stages of human T1D.

HIRN-CBDS:
Research Objectives and Scope

The exploration of the specific events responsible for beta
cell failure and destruction at the onset of human T1D has been hampered by the
lack of two important sets of tools:

Highly-specific, highly-sensitive and highly-quantitative biomarkers
of human beta cell stress or beta cell death, that can detect subtle changes in
the status of beta cell health during the asymptomatic phase of the disease,
and allow the reliable and early staging of individuals at risk of developing
autoimmune diabetes.

Technologies for the detailed and integrated molecular analyses
of human pancreata at the cellular and sub-cellular level, that can help
identify molecular signatures, metabolic profiles and the activation of
specific disease pathways in the subsets of islets and beta cells that are
poised for selective damage or destruction early in the disease process.

Contributions relevant to this initiative are therefore restricted
to the following two areas of research:

1) Development of specific biomarkers of human beta cell
stress or beta cell death in asymptomatic T1D:

Most discoveries to find non-invasive biomarkers of beta
cell stress or beta cell death involve the use of omics-based screens to look
for bio-products that vary significantly between samples taken from Type 1
diabetic and control subjects, or between samples taken at different stages of
T1D progression in individual patients. But as noted above, the asymptomatic
phase of T1D in humans is characterized by slowly developing and relatively
subtle changes, such as the stress or destruction of only a subset of beta
cells in only a subset of pancreatic islets at any given point in time. These
biological events may be relatively insignificant in the context of all other
physiological changes occurring daily in the human body, and are therefore
unlikely to leave strong biological signatures that can be detected using
standard approaches that rely on global molecular analysis of body fluids or of
the whole pancreatic tissue.

A more promising strategy may be to identify molecular
signatures or cell-processed products that are highly-specific of beta cell
identity or beta-cell stress, and to look for their presence in the body fluids
(blood, urine, saliva) of individuals who are either at-risk or
newly-diagnosed. Relevant biomarkers may include epigenetically-modified
genomic DNA regions that are released in the blood stream by dying beta cells;
mechanistically informative modified products (such as proteins, peptides,
nucleic acids) secreted or excreted by stressed beta-cells; circulating free or
exosome-encapsulated microRNAs specifically released by stressed beta cells; or
antibodies against rare neo-antigens created as a result of early beta cell
stress or injury early in the disease process. This initiative will support the
identification and validation of such biomarkers in human samples, and the
development of related detection assays that can be used safely in humans.
Relevant applications need to propose the development of biomarkers and assays
that can detect human beta cell stress, injury or death non-invasively, in a
quantitative, specific and sensitive manner, to such a degree that they provide
an accurate and reliable prediction of the progression to autoimmunity in
asymptomatic at-risk individuals.

2) Development of tools for the exploration of islet
heterogeneity, stress and plasticity in human pancreata:

Given the recent availability of high-quality collections of
pancreata from cadaveric organ donors, investigators interested in studying T1D
natural history and pathogenesis have not yet had the opportunity to develop sophisticated
analytical tools to extract meaningful biological information from challenging
biospecimens such as frozen or paraffin-embedded tissue slices. In other areas
of biology however, such as cancer or brain research, many of these
technologies are being developed, and could be applied or modified to study
archived human pancreata. For example, laser-guided microdissection protocols
allow the recovery of just a few selected cells from minute amounts of tissues.
The dissected cells can then be used for a variety of investigations such as
transcriptomic, epigenomic, proteomic or metabolomic studies, as well as T-cell
epitope mapping, using technologies such as whole exosome sequencing, pathology
tissue chromatin immunoprecipitation (PAT-ChIP), ion semiconductor sequencing
(ISS), matrix-assisted laser desorption/ionization (MALDI), combinatorial
peptide-MHC multimer staining and mass cytometry and single-cell omics analyses.
Other type of analyses such as multiplexed fluorescence microscopy allow for the
quantitative characterization of dozens of analytes simultaneously (including peptides,
proteins and nucleic acids), with single-cell and subcellular definition, and
across the entire tissue.

This initiative will support the development or adaptation
of emerging technologies for the biological and molecular exploration of
archived human pancreata. It will also support the use of these advanced tools
to answer key biological questions related to the development of T1D such as:
do beta cells contribute to their own destruction/disappearance and if so, how?
Does beta cell stress occur at different stages of human T1D and if so, does it
result in specific molecular signatures? Does beta cell stress initiate or
perpetuate autoimmunity? Does beta cell de-differentiation occur in human T1D
and if so, does it contribute to resolve beta cell stress? Why are some islets spared
from insulitis in the pancreata of so many T1D patients? What is the
contribution of the various islet cell types to disease progression before,
during and after insulitis? Is the exocrine pancreas involved in islet invasion?
Does beta cell regeneration occur in concert with beta cell destruction in
subjects with islet autoimmunity? Can other islet cells contribute to a
replenishment of the beta cell mass once the inflammation has subsided? What
are the specific characteristics of the residual pools of beta cells found in
many patients with long-term T1D? Can specific epigenetic signatures be used in
the context of fixed human pancreata to identify sub-populations of islet cells
that are phenotypically identical, but may result from distinct lineage
histories and may contribute differently to the disease process? Can
single-cell sequencing and single-cell proteomics allow the functional states
of individual islet cells to be analyzed, help uncover cell lineage
relationships, or lead to the discovery of early biomarkers of beta cell stress
and injury? Can post-translational modification of autoantigens in stressed
beta cells allow autoreactive T-cells to escape immune tolerance, thereby
priming the autoimmune process?

The use of animal models in combination with the study of
human samples, such as lineage tracing experiments in the NOD mouse or
xenograft models using transplanted human islets or tissues, may be required in
order to achieve some of the goals described in this initiative, and will be
permitted. However, applications proposing to perform primarily mechanistic
studies in the mouse, with only a few validation experiments in human tissues,
will not be considered responsive to this announcement and will not be reviewed.

In choosing a source of human biospecimens, applicants are
encouraged to use high-quality repositories, biobanks and procurement networks,
whether they are linked to NIDDK-funded clinical studies such as the Diabetes Prevention
Trial-Type 1 (DPT-1) or the Type 1 Diabetes Trialnet (https://www.niddkrepository.org/niddk/home.do ), or supported by private research efforts such as the JDRF nPOD (http://www.jdrfnpod.org/ ) or the T1D
Exchange (http://www.t1dexchange.org/ ). If available, pancreata that are either densely genotyped (such as from
NIH-supported the GTEx collection: https://commonfund.nih.gov/GTEx/overview.aspx ) or originating from donors with well-documented disease history or health
records, should be used.

Applicants may decide to address one or both of the two
priority areas described above. The assembly of multidisciplinary teams under a
single application to address the scientific challenges outlined in this
initiative is encouraged, particularly if they combine different expertise (such
as beta cell biology, immunology, experience with state-of-the-art analytical
tools or technologies). But single-investigator applications from individuals
with the required expertise to make a major contribution are also welcome.
Regardless of the team-structure and composition of the initial UC4
application, all CBDS investigators will be expected to work collaboratively
with all of their CBDS and HIRN colleagues and to contribute to an environment
of sharing and trust across the network.

All methods, reagents, resources, biomaterials, protocols, data
and models developed by CBDS investigators are expected to be made available to
the research community. Because the individual UC4 projects will be coordinated
through CBDS, the timeline and processes for sharing within CBDS and with the
community at large will be established by the CBDS NIDDK Project Scientist or
the CBDS Steering Committee. All participants will be expected to adhere to
these policies as a term of the award. Policy documents for CBDS will be
accessible on the HIRN website.

Meetings
of CBDS and HIRN

CBDS Program Director(s)/Principal Investigator(s)
(PD(s)/PI(s)) must participate in an initial in person HIRN meeting soon after
awards are made, in the annual HIRN Investigator Scientific Retreat, as well as
in CBDS Steering Committee teleconferences to be held at least bi-annually.
All participants will be obligated to abide by the policies adopted the
majority vote of the CBDS Steering Committee. In the application, research
project budget requests must include costs for the PD/PI and up to two other
members of the individual project to attend both the initial in-person HIRN
meeting and the annual HIRN Investigator Scientific Retreat. The annual HIRN
Investigator Scientific Retreat will last 2-3 days. All CBDS teleconferences
will be organized and administered by the HIRN-CC to coordinate the research
projects to be conducted by the research grantees. Note that the HIRN-CC will
support costs of all CBDS and HIRN-related meetings except for costs for research
project investigators to travel and attend the meetings. The HIRN-CC is also responsible
for providing and maintaining a record of minutes of all CBDS meetings, which
will be approved by the CBDS Steering Committee.

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there
will be substantial Federal scientific or programmatic involvement.
Substantial involvement means that, after award, NIH scientific or program
staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New

The OER
Glossary and the SF424 (R&R) Application Guide provide details on
these application types.

Funds Available and Anticipated Number of Awards

NIDDK intends to commit $9 million to fund 2-4 awards
in FY2014.

Award Budget

Application budgets are limited to $600,000 per year in
direct costs. This limit is inclusive of any direct and F&A costs
associated with consortium or subcontract agreements.

Award Project Period

The maximum project period is five years.

NIH grants policies as
described in the NIH Grants
Policy Statement will apply to the
applications submitted and awards made in response to this FOA.

Section III. Eligibility
Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:

Applicant organizations must complete and maintain the
following registrations as described in the SF 424 (R&R) Application Guide
to be eligible to apply for or receive an award. All registrations must be
completed prior to the application being submitted. Registration can take 6
weeks or more, so applicants should begin the registration process as soon as
possible. The NIH
Policy on Late Submission of Grant Applications states that failure to
complete registrations in advance of a due date is not a valid reason for a
late submission.

Dun and Bradstreet
Universal Numbering System (DUNS) - All registrations require that
applicants be issued a DUNS number. After obtaining a DUNS number, applicants
can begin both SAM and eRA Commons registrations. The same DUNS number must be
used for all registrations, as well as on the grant application.

System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least
annually. The renewal process may require as much time as the
initial registration. SAM registration includes the assignment of a Commercial
and Government Entity (CAGE) Code for domestic organizations which have not
already been assigned a CAGE Code.

eRA Commons - Applicants
must have an active DUNS number and SAM registration in order to complete the
eRA Commons registration. Organizations can register with the eRA Commons as
they are working through their SAM or Grants.gov registration. eRA Commons
requires organizations to identify at least one Signing Official (SO) and at
least one Program Director/Principal Investigator (PD/PI) account in order to
submit an application.

Grants.gov – Applicants
must have an active DUNS number and SAM registration in order to complete the
Grants.gov registration.

Program
Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account and should
work with their organizational officials to either create a new account or to
affiliate an existing account with the applicant organization’s eRA Commons
account. If the PD/PI is also the organizational Signing Official, they must
have two distinct eRA Commons accounts, one for each role. Obtaining an eRA
Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal
Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the
same as one already reviewed within the past thirty-seven months (as described
in the NIH
Grants Policy Statement), except for submission:

To an RFA of an application that was submitted previously as an
investigator-initiated application but not paid;

Of an investigator-initiated application that was originally submitted
to an RFA but not paid; or

Of an application with a changed grant activity code.

Section IV. Application and Submission Information

1. Requesting an
Application Package

Applicants must download the SF424 (R&R) application
package associated with this funding opportunity using the “Apply for Grant
Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

Although a letter of intent is not required, is not binding,
and does not enter into the review of a subsequent application, the information
that it contains allows IC staff to estimate the potential review workload and
plan the review.

By the date listed in Part 1. Overview
Information, prospective applicants are asked to submit a letter of intent
that includes the following information:

All page limitations described in the SF424 Application Guide
and the Table
of Page Limits must be followed.

Required and Optional Components

The forms package associated with this FOA includes all
applicable components, required and optional. Please note that some components
marked optional in the application package are required for submission of
applications for this FOA. Follow all instructions in the SF424 (R&R)
Application Guide to ensure you complete all appropriate “optional” components.

Instructions for Application Submission

The following section supplements the instructions found in
the SF424 (R&R) Application Guide and should be used for preparing an
application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

PDs/PIs should provide evidence of prior experience working
productively in collaborative programs.

R&R Budget

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Budget requests must include costs for the PD/PI and up to two
other members of the individual project to attend both the initial in-person
HIRN meeting and the annual HIRN Investigator's Scientific Retreat.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Resource
Sharing Plan: Individuals are required to comply with the
instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model
Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424
(R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs
requested for any one year, should address a Data Sharing Plan.

NIH policy expects that grant recipients make unique research
resources readily available for research purposes to qualified individuals
within the scientific community after publication. Investigators responding to
this funding opportunity should include a resource sharing plan addressing how
unique research resources will be shared or explain why sharing is not
possible.

Availability
of technologies and protocols developed with funds from this award.

Appendix: Do not use the Appendix to circumvent page limits. Follow all
instructions for the Appendix as described in the SF424 (R&R) Application
Guide.

Planned Enrollment Report

When conducting clinical research, follow all instructions
for completing Planned Enrollment Reports as described in the SF424 (R&R)
Application Guide.

PHS 398 Cumulative Inclusion Enrollment Report

When conducting clinical research, follow all instructions
for completing Cumulative Inclusion Enrollment Report
as described in the SF424 (R&R) Application Guide.

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies
described in the NIH Grants
Policy Statement, and procedures for foreign institutions described
throughout the SF424 (R&R) Application Guide.

3. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications
before the due date to ensure they have time to make any application
corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants
across all Federal agencies). Applicants must then complete the submission process by tracking the
status of the application in the eRA Commons, NIH’s electronic system for grants administration.
NIH and Grants.gov systems check the application against many of the
application instructions upon submission. Errors must be corrected and a
changed/corrected application must be submitted to Grants.gov on or before the application
due date. If a Changed/Corrected application is submitted after the deadline,
the application will be considered late.

Applicants
are responsible for viewing their application before the due date in the eRA
Commons to ensure accurate and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

Since these awards will be issued with a 5-year budget and
project period from the same fiscal year, the grantee will not have any
authority for an automatic extension nor will one be permitted with NIH prior
approval. Funds will not be available for expenditure beyond September 30 of
the 5th fiscal year after the period of availability. Thus, extensions of the
budget/project period will not be allowed.

6. Other Submission
Requirements and Information

Applications must be submitted electronically following the
instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically.

Important
reminders:All PD(s)/PI(s) must include their eRA Commons ID in the
Credential fieldof the Senior/Key Person Profile Component of the
SF424(R&R) Application Package. Failure to register in the Commons
and to include a valid PD/PI Commons ID in the credential field will prevent
the successful submission of an electronic application to NIH. See Section III of this FOA for information on
registration requirements.

The applicant organization must ensure that the DUNS number it provides on the
application is the same number used in the organization’s profile in the eRA
Commons and for the System for Award Management. Additional information may be
found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for
completeness by the Center for Scientific Review and responsiveness by NIDDK,
NIH. Applications that are incomplete and/or nonresponsive will not be
reviewed.

In order to expedite review, applicants are requested to
notify the NIDDK Referral Office by email at calvof@mail.nih.gov when the application has been submitted. Please include the FOA number and
title, PD/PI name, and title of the application.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-13-030.

Section V. Application Review Information

1.
Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

Overall Impact

Reviewers will provide an overall impact score to reflect
their assessment of the likelihood for the project to exert a sustained,
powerful influence on the research field(s) involved, in consideration of the
following review criteria and additional review criteria (as applicable for the
project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other
researchers well suited to the project? If Early Stage Investigators or New
Investigators, or in the early stages of independent careers, do they have
appropriate experience and training? If established, have they demonstrated an
ongoing record of accomplishments that have advanced their field(s)? If the
project is collaborative or multi-PD/PI, do the investigators have
complementary and integrated expertise; are their leadership approach,
governance and organizational structure appropriate for the project? Do PD(s)/PI(s)
provide evidence of experience working productively in collaborative
environments? Do PD(s)/PI(s) provide documented evidence of experience sharing
data and reagents with the research community?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be
managed?

If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact score, but will not give
separate scores for these items.

Collaborative Research
Opportunities:

Does the project present an opportunity for research
that would be enhanced by consortium interaction, collaboration and expertise?

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to subjects,
2) adequacy of protection against risks, 3) potential benefits to the subjects
and others, 4) importance of the knowledge to be gained, and 5) data and safety
monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Guidelines
for the Review of Human Subjects.

Inclusion of Women, Minorities, and
Children

When the proposed project involves clinical research,
the committee will evaluate the proposed plans for inclusion of minorities and
members of both genders, as well as the inclusion of children. For additional
information on review of the Inclusion section, please refer to the Guidelines
for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of
veterinary care; 4) procedures for limiting discomfort, distress, pain and
injury to that which is unavoidable in the conduct of scientifically sound
research including the use of analgesic, anesthetic, and tranquilizing drugs
and/or comfortable restraining devices; and 5) methods of euthanasia and reason
for selection if not consistent with the AVMA Guidelines on Euthanasia. For
additional information on review of the Vertebrate Animals section, please
refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact score.

Applications from Foreign
Organizations

Reviewers will assess whether the project presents
special opportunities for furthering research programs through the use of
unusual talent, resources, populations, or environmental conditions that exist
in other countries and either are not readily available in the United States or
augment existing U.S. resources. .

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will consider whether the budget and the
requested period of support are fully justified and reasonable in relation to
the proposed research.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s)convened by the NIDDK, in
accordance with NIH peer
review policy and procedures, using the stated review
criteria. Assignment to a Scientific Review Group will be shown in the eRA
Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall impact
score.

Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in
response to this FOA. .

Applications will be assigned to the appropriate NIH
Institute or Center. Applications will compete for available funds with all
other recommended applications submitted in response to this FOA. Following
initial peer review, recommended applications will receive a second level of
review by the National Diabetes and Digestive and Kidney Diseases Advisory
Council. The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement
and Award Dates

After the peer review of the application is completed, the
PD/PI will be able to access his or her Summary Statement (written critique)
via the eRA
Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH Grants
Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

The following special terms of award are in addition to, and
not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant
administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable
when State and local Governments are eligible to apply), and other HHS PHS, and
NIH grant administration policies.

The administrative and funding instrument used for this
program will be the cooperative agreement UC4, an "assistance"
mechanism (rather than an "acquisition" mechanism), in which
substantial NIH programmatic involvement with the awardees is anticipated
during the performance of the activities. Under the cooperative agreement, the
NIH purpose is to support and stimulate the recipients' activities by
involvement in and otherwise working jointly with the award recipients in a
partnership role; it is not to assume direction, prime responsibility, or a
dominant role in the activities. Consistent with this concept, the dominant
role and prime responsibility resides with the awardees for the project as a
whole, although specific tasks and activities may be shared among the awardees
and the NIH as defined below.

The
PD(s)/PI(s) will have the Primary Responsibility for:

The awardee will be primarily responsible for defining the
objectives and approaches, planning, conduct, analysis, and publication of
results, interpretations, and conclusions of studies conducted under the terms
and conditions of the cooperative agreement award.

The Principal Investigator/Program Director will assume
responsibility and accountability to the applicant organization officials and
to the NIH for the performance and proper conduct of the research supported
under this Funding Opportunity Announcement in accordance with the terms and
conditions of award, as well as all pertinent laws, regulations and policies.

The awardee will retain custody of and have primary rights to the
data and software developed under these awards, subject to Government policies
regarding rights of access consistent with current HHS, PHS, and NIH policies.

All staff of the Awardee will maintain the confidentiality of the
information developed by the investigations, including, without limitation,
study protocols, data analysis, conclusions, etc. per policies approved by the
consortium as well as any confidential information received by third party
collaborators.

Awardees must analyze, publish and/or publicly release and
disseminate results, data and other products of the study in a timely manner,
concordant with the approved plan for making quality-assured data and materials
available to the scientific community and the NIH, consistent with NIH policies
and goals of the FOA.

All staff of the Awardee will be required to participate in a
cooperative and interactive manner with NIH staff, one another and with the
HIRN-AH in all aspects of CBDS.

Awardees must share data, materials, models, methods, information
and unique research resources that are generated by the projects in accordance
with CBDS policies in order to facilitate progress. When appropriate, and in
accordance with NIH policies, awardees will be expected to collaborate; share
novel reagents, biomaterials, methods and models and resources; and share both
positive and negative results that would help guide the research activities of
other CBDS members.

Awardees will submit a list of milestones and project
deliverables to the HIRN CC prior to the initial HIRN meeting, and will update
this list annually.

CBDS Awardees agree to establish agreements amongst themselves
that address the following issues: (1) procedures for data sharing among
consortium members and data sharing with industry partners; (2) procedures for
safeguarding confidential information, including without limitation, any data
generated by the consortium as well as information and/or data received from
external collaborators; (3) procedures for addressing ownership of intellectual
property that result from aggregate multi-party data; (4) procedures for
sharing biospecimens under an overarching MTA amongst consortium members that
operationalizes material transfer in an efficient and expeditious manner; (5)
procedures for reviewing publications, determining authorship, and industry
access to publications.

Awardees agree that industry collaborations should be governed by
a research collaboration agreement (e.g. CTA, RCA, etc.) with terms that ensure
the collaboration is conducted in accordance with the Cooperative Agreement,
applicable NIH policies and procedures and any policies and procedures
developed by the CBDS.

Awardees must operate in accordance with processes and goals as
delineated in the Funding Opportunity Announcement.

Upon completion or termination of the research project(s), the
awardees are responsible for making all study materials and procedures broadly
available (e.g., putting into the public domain) or making them accessible to
the research community according to the NIH-approved plan submitted for each
project, for making data and materials available to the scientific community
and the NIH for the conduct of research. The data sharing plan should include
a plan to accomplish this at the end of the study.

Awardees may be asked by NIH staff to scientifically review
applications for special opportunity pool funds, as deemed appropriate.

NIH
Staff have Substantial Programmatic Involvement that is above and beyond the
normal stewardship role in awards, as described below:

The NIDDK will designate program staff, including a Program
Officer and a Grants Management Specialist to provide stewardship and
administrative oversight of the cooperative agreement. The Program Officer and
Grants Management Specialist will be named in the Notice of Grant Award.

The NIH will invite experts with relevant scientific expertise to
provide feedback to the NIH on CBDS activities. The External Experts will meet
to review the progress of the research projects and to advise NIH staff of
scientific developments and opportunities that may enhance the achievement of
the study goals.

An NIDDK Project Scientist will be substantially involved in this
project above and beyond the normal stewardship of an NIDDK Program Official as
follows:

The NIH
Project Scientist will coordinate and facilitate the research projects, attend
and participate in all meetings of the CBDS, and act as a liaison between the
Awardee and the External Experts.

The NIH
Project Scientist and Program Officer will review the scientific progress,
cooperation in carrying out research, and maintenance of high quality research
in each of the individual research project, and review the project for
compliance with operating policies developed by the CBDS. Based on this
review, the Project Scientist in conjunction with the Program Officer may
recommend to the NIH to continue funding, or to withhold or restrict support
for lack of scientific progress or failure to adhere to policies established by
the CBDS. Review of progress may include regular communications between the
Principal Investigator and NIH staff, periodic site visits for discussions with
awardee research teams, fiscal review, and other relevant matters. The NIH
retains the option of organizing periodic external review of progress.

The NIDDK reserves the right to terminate or curtail any study or
any individual award in the event of (1) substantial shortfall in data
collection or submission, quality control, or other major breach or a study
protocol or CBDS policy and procedure, (2) substantive changes in a study
protocol that are not in keeping with the objectives of the FOA, and/or (3)
concerns related to human subject safety that prompt the need for premature
termination.

The NIH Program Scientist and Program Officer will review applications
for Special Opportunity Funds for responsiveness to program goals to insure
that they are within the scope of CBDS research as described in the Funding
Opportunity Announcement and NIH guidelines. The NIH will enlist additional
scientific consultants as necessary from within the NIH whose function will be
to assist the Project Scientist in carrying out the goals and aims of the
approved studies. The NIH will have one vote for any key committees,
regardless of the number of NIH consultants involved in the project.

The NIH Project Scientist will have substantial scientific
programmatic involvement in research coordination and performance monitoring.
The dominant role and primary responsibility for these activities resides with the awardee,
however, specific tasks and activities in carrying out the studies will be
shared among the awardees and the NIH Project Scientist.

The NIH Project Scientist serves as a resource with respect to
other ongoing NIH activities that may be relevant to CBDS studies to facilitate
compatibility and avoid unnecessary duplication of effort.

The NIH Project Scientist or designee may coordinate activities
among awardees by assisting in the design, development, and coordination of a
common research protocol and statistical evaluations of data and in the
publication of results.

The NIH Project Scientist may be a co-author on study
publications. In general, to warrant co-authorship, the NIH staff must have
contributed to one or more of the following areas: (a) design of the concepts
or experiments being tested; (b) performance of significant portions of the
activity; (c) participation in analysis and interpretation of study results and
(d) preparation and authorship of pertinent manuscripts.

Areas
of Joint Responsibility include:

Through the Awardees and NIH staff, CBDS will cooperatively
develop and implement processes to submit information and data to the HIRN-AH,
determine criteria and processes for quality control of information and data to
be posted for the research community, refine scientific objectives, and
implement research advances to facilitate the goals of the study, consistent
with NIH policies and achieving the goals of the program as described in the
Funding Opportunity Announcement. There will be an initial face-to-face meeting
of HIRN and a minimum of 2 CBDS meetings (teleconferences or face-to face
meetings) annually. CBDS awardees, the CBDS Project Scientist, and the CBDS
Program Official are expected to attend these meetings. One of these bi-annual
meetings could be combined with the annual HIRN Investigator Scientific
Retreat.

Steering
Committee

CBDS awardees agree to the governance of the CBDS through a
Steering Committee.

On an annual basis, and following input from the CBDS Steering
Committee members, NIDDK staff will appoint a Steering Committee Chair who will
be in charge of facilitating the CBDS Steering Committee meetings and
teleconferences. In collaboration with the HIRN-CC and the NIH Project
Scientist, the Chairperson is responsible for coordinating the Steering
Committee activities, for preparing meeting agendas and for chairing meetings.

The Steering Committee, including the Project Scientist, is
responsible for establishing and implementing processes and criteria for
recommending special projects for consideration for special opportunity funds
by NIH staff.

The NIH Project Scientist may work with awardees on issues coming
before the Steering Committee and, as appropriate, other committees.

The Steering Committee will be composed
of the Principal Investigators/Program Directors for each UC4, or by UC4
representatives (one per UC4 grant) chosen by the Principal
Investigators/Program Directors in the cases of multi-PI grants, and the NIH
Project Scientist. Only the UC4 PI/PD or multi-PI UC4 representatives and the
NIH Project Scientist will be voting members of the Steering Committee and will
attend all meetings of the Steering Committee. Each full member will have one
vote. Other designated NIH program staff attending the steering committee
meetings will be ex officio (non-voting) members. The CBDS Steering Committee
will meet at least twice a year.

All major scientific and policy decisions will be determined by
voting policies as established by the Steering Committee at the initial
meeting. This committee will operate to develop collaborative protocols,
identify impediments to success and strategies to overcome them, develop shared
tools for disseminating information about the projects, and identify
opportunities for sharing techniques, materials, information and tools
developed within each individual project. Steering Committee activities and
decisions will consider the advice of the External Experts.

The NIH Project Scientist will help the Steering Committee
develop and draft operating policies.

NIDDK staff, in concert with the Steering Committee, will have
the option to redirect research activities being pursued within the UC4 grants if
it is considered beneficial to the overall program.

The awardee will be responsible for accepting and implementing
the goals, priorities, procedures, protocols, and policies agreed upon by the
Steering Committee and Subcommittees.

Awardees must serve on CBDS subcommittees as needed.
Subcommittees will report progress at Steering Committee Meetings and/or lead
discussions at the Annual Investigator’s Retreat.

HIRN
Trans-Network Committee (HIRN-TNC)

The HIRN-TNC will consist of: the PD/PI of the HIRN CC, the PD/PI
of the HIRN BC, and the Steering Committee Chairs and Project Scientists of the
HIRN scientific topic consortia (CHIB, CTAR, CMAI, and CBDS); the TNC is not a
governing body and does not cast votes.

The TNC will facilitate communication and foster collaboration
across the different consortia.

The TNC will be responsible for organizing the yearly HIRN
Scientific Investigator’s Retreat.

The TNC will meet by teleconference at least twice a year and
will be organized by the HIRN CC. Meetings will be used to discuss and
prioritize, and review the progress of applications that will use
"opportunity pool" funds. Subcommittees of HIRN, as well as working
groups for scientific planning may be established and require participation by
the CBDS members through in-person, electronic, or teleconference meetings, as
appropriate. The HIRN CC is responsible for providing and maintaining a record
of minutes of all EC meetings, which will be approved by the EC.

Expert
Scientific Panel (ESP)

An independent panel of 2-5 External Experts will be appointed
by the NIDDK and meet by teleconference with the CBDS Project Scientist and the
CBDS Project Officer at least once a year. The CBDS-ESP will be updated on
progress and give feedback to NIH on adjustments and future directions for the
CBDS research projects. On an annual basis, and following input from the ESP
members, NIDDK staff will appoint an ESP Chair who will be required to attend
the annual HIRN Investigator Scientific Retreat, to participate to the CBDS
Steering Committee meetings as ex-officio, and to serve as the CBDS-ESP
representative to the larger HIRN-ESP that will also meet once a year. The CBDS-ESP
Chair will be tasked with relaying the CBDS Steering Committee recommendations
for new Opportunity Funds Initiatives to the HIRN-ESP. All CBDS-ESP members
will also be invited to listen as ex-officio to CBDS Steering Committee
meetings. Members of the CBDS-ESP may be asked, on an ad hoc basis, in the peer
review of applications for new research applications that request “opportunity
pool” funds. The HIRN-CC will support costs for teleconferences between the ESP
and the CBDS Steering Committee, will arrange the CBDS-ESP and HIRN-ESP
teleconferences, maintain a record of minutes, and support costs for the CBDS-ESP
chair to participate in the annual HIRN Investigator Scientific Retreat.

Dispute
Resolution

Disagreements that may arise in scientific/technical matter
or programmatic matters (within the scope of the award) between award
recipients and the NIDDK may be brought to arbitration after first attempting
to resolve the issue through the Steering Committee or its subcommittees, as
appropriate. An Arbitration Panel composed of three members will be convened.
It will have three members: a designee of the Steering Committee chosen without
NIH staff voting, one NIH designee, and a third designee with expertise in the
relevant area who is chosen by the other two; in the case of individual
disagreement, the first member may be chosen by the individual awardee. This
special dispute resolution procedures in no way affect the awardee's right to
appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50,
Subpart D, and HHS regulations at 45 CFR Part 16.

3. Reporting

Progress reports for multi-year funded awards are due
annually on or before the anniversary of the budget/project period start date
of award. The reporting period for multi-year funded award progress report is
the calendar year preceding the anniversary date of the award. Information on
the content of the progress report and instructions on how to submit the report
are posted at http://grants.nih.gov/grants/policy/myf.htm

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in the NIH Grants
Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants
Policy Statement for additional information on this reporting
requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and
405 of the Public Health Service Act as amended (42 USC 241 and 284) and under
Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.